Astaxanthin provides neuroprotection in an experimental model of traumatic brain injury via the Nrf2/HO-1 pathway.

BACKGROUND Astaxanthin (ATX) is a carotenoid pigment with effective antioxidant, anti-inflammatory, antitumor and immunomodulatory actions. ATX has been proposed to exert neuroprotective effects and attenuate oxidative stress in mice after traumatic brain injury (TBI). The nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase 1 (HO-1) signaling pathway is stimulated after TBI and activates a compensatory mechanism against TBI. Nevertheless, the effect of ATX on the pathophysiology of TBI in mice is limited. Our present study evaluated the neuroprotection afforded by ATX and the possible role of the Nrf2/HO-1 pathway in experimental TBI. MATERIALS AND METHODS Mice were casually separated into 3 groups: the sham, TBI + vehicle, and TBI + ATX (100 mg/kg, intraperitoneally administered) groups. Neurobehaviors of the mice were assessed using the neurological severity scores (NSSs), the forced swimming test (FST) and the rotarod test. Levels of the Nrf2, HO-1, NAD(P)H: quinine oxidoreductase-1 (NQO1), cleaved caspase3 (C-caspase3), and superoxide dismutase1 (SOD1) proteins and levels of the Nrf2 and HO-1 mRNAs were assessed. In addition, Nrf2 nuclear import and apoptosis were measured after TBI. RESULTS The ATX treatment significantly improved the neurological status, promoted Nrf2 activation, and upregulated the expression of the Nrf2 and HO-1 mRNAs and the levels of the Nrf2, HO-1, and NQO1 proteins after TBI. The level of the SOD1 protein was decreased after TBI and increased after ATX treatment; however, the difference was not significant. ATX markedly reduced the level of the C-caspase3 protein and the number of TUNEL-positive cells, indicating that it exerted an antiapoptotic effect. Immunofluorescence staining confirmed that ATX promoted Nrf2 nuclear import. CONCLUSIONS Based on our study, ATX possibly affords neuroprotection by activating the Nrf2/HO-1 signaling pathway in mice after TBI.